Humoral correlates of clinical response to thymectomy in myasthenia gravis

Mechanisms by which thymectomy confers its clinical benefit in patients with AChR-antibody (Ab) positive myasthenia gravis (MG) remain poorly understood. We used a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to identify Ab-features that track with clinical response to thymectomy in 78 patients with AChR-Ab positive MG, recruited during the MGTX trial, an NIH-sponsored randomized, controlled study of thymectomy plus prednisone versus prednisone alone. Clinically meaningful improvement was defined as a change of at least 3 points on the quantitative MG scale at month 36 compared to baseline. AChR-specific immunoglobulin G (IgG) titers decreased in patients experiencing clinical improvement but remained stable in patients with poor response to therapy. Thymectomized patients showed an accelerated decline in AChR-specific IgG titers. At month 36, the frequency of digalactosylated and monosialylated total IgG Fc-glycans was increased in thymectomized responders compared to non-responders. Fc-glycosylation profiles were unchanged in prednisone only treated patients with or without clinically meaningful improvement. Clinical benefit achieved by thymectomy is strongly associated with an anti-inflammatory IgG Fc-glycosylation profile.